Critical components for designing and implementing randomized controlled trials

Randomized controlled trials (RCTs) are considered the first level of evidence to assess the efficacy of novel interventions/therapies.Proper design and implementation of an RCT can result in convincing causal inferences.RCTs often represent the gold standard for clinical trials when appropriately designed,conducted and reported.However,there are limitations in implementation of RCTs,including sufficiency of randomized allocation (especial for allocation concealment),implementing standard intervention,maintaining follow-up and statement of conflicting interests.Therefore,the basic principles of RCTs are outlined here so that pediatric investigators can further understand what is the best evidence based on RCTs.More importantly,the quality of pediatric RCTs may be improved by following challenges in pediatric clinical trials outlined here.

Prenatal and perinatal risk factors for solid childhood malignancies: A questionnaire-based study

Importance:Childhood solid tumors account for the highest proportion of childhood cancers and are one of the leading causes of death in childhood.However,their pathogenesis is unclear.Objective:To explore prenatal and perinatal risk factors for solid malignancies in children.Methods:We enrolled 71 consecutive pediatric patients (44 boys and 27 girls;median age,30 months) with solid tumors who were diagnosed and treated at our center from January 2013 to December 2016 as the case group.We also enrolled 211 age-and residence-matched healthy children (ratio of approximately 3:1 with the case group) as the control group.We conducted a questionnaire-based survey with the parents of these 282 children.Univariate and multivariate conditional logistic regression analyses of the collected data were performed.Results:Confirmed solid malignancies included neuroblastoma (n =32),rhabdomyosarcoma (n =18),retinoblastoma (n =7),renal tumors (n =3),and other tumors (n =11).Risk factors for solid childhood tumors in the univariate analysis were the parents' age,gravidity,parity,abortion history,vaginal bleeding,family history of malignancy,and prenatal use of folic acid or hematinics/iron supplements (P ＜ 0.05),and those in the multivariate analysis were higher parity (odds ratio [OR],2.482;95％ confidence interval [CI],1.521-4.048),family history of malignancy (OR,3.667;95％ CI,1.679-8.009),and prenatal use of hematinics/iron supplements (OR,2.882;95％ CI,1.440-5.767).In contrast,use of prenatal folic acid was protective (OR,0.334;95％ CI,0.160-0.694).Interpretation:A family history of malignancy,use of prenatal hematinics/iron supplements,and higher parity are risk factors for solid childhood tumors,whereas use of prenatal folic acid is a protective factor.

Phenomapping approach to interpreting coronary dimensions in febrile children

Importance:Coronary artery dilation may occur in febrile children with and without Kawasaki disease(KD).Objective:We explored the application of unsupervised learning algorithms in the detection of novel patterns of coronary artery phenotypes in febrile children with and without KD.Methods:A total of 239 febrile children(59 non-KD and 180 KD patients),were recruited.Unsupervised hierarchical clustering analysis of phenotypic data including age,hemoglobin,white cell count,platelet count,C-reactive protein,erythrocyte sedimentation rate,albumin,alanine aminotransferase,aspartate aminotransferase,and coronary artery z scores were performed.Results:Using a cutoff z score of 2.5,the specificity was 98.3%and the sensitivity was 22.1%for differentiating non-KD from KD patients.Clustering analysis identified three phenogroups that differed in a clinical,laboratory,and echocardiographic parameters.Compared with phenogroup I,phenogroup III had the highest prevalence of KD(91%),worse inflammatory markers,more deranged liver function,higher coronary artery z scores,and lower hematocrit and albumin levels.Abnormal blood parameters in febrile children with z scores of coronary artery segments<0.5 and 0.5–1.5 was associated with increased risks of having KD to 8.7(P=0.003)and 4.4(P=0.002),respectively.Interpretation:Phenomapping of febrile children with and without KD identified useful laboratory parameters that aid the diagnosis of KD in febrile children with relatively normal-sized coronary arteries.

Better reporting quality for improved pediatric investigation:Application of health research reporting guidelines

Clinical research on the accuracy of diagnostic tests,the power of prognostic markers,and the efficacy and safety of interventions are the cornerstone of evidence-based health care.1 Transparency and sufficient reporting are important for conveying research findings to the public,practitioners,and students in medicine because insufficient reporting of results would hinder assessment for a study’s strengths and weaknesses and thus hamper integration of evidence,even from well-conducted research.2 However,the reporting quality of articles in most healthcare journals remains inadequate.

Validity of web-based self-assessment of pubertal development against pediatrician assessments

Importance:A web-based instrument for self-assessment of puberty could be convenient and feasible for large-scale multicenter populationbased epidemiological studies for Tanner stages evaluation.Objective:To validate web-based self-assessment of pubertal development against assessment by a pediatrician.Methods:Outpatients aged 8-18 years were consecutively recruited in the endocrinology department of Beijing Children's Hospital from October 2016 to August 2017.A web-based self-assessment instrument for pubertal development was introduced to participants by an appointed pediatrician.Tanner stage of puberty was self-assessed by participants in a private environment.Participants were then examined by a senior pediatrician underwent blinded assessment.Weighted kappa and Spearman correlation analyses were conducted to evaluate agreement.The accuracy of the web-based instrument for self-assessment of pubertal onset was evaluated according to sensitivity,specificity,positive predictive value and negative predictive value.Results:A total of 174 participants (including 82 girls and 92 boys)were assessed consecutively.Correlation coefficients were 0.872 for pubic hair and 0.933 for testicular volume (P<0.001) among boys;a similar result was obtained for the weighted kappa value (0.825).For girls,the correlation coefficient and weighted kappa for pubic hair was 0.785 and 0.878,respectively.However,breast self-assessment had a medium level of agreement with pediatrician assessment (weighted kappa,0.495;correlation coefficient,0.643).Moreover,the accuracy of self-assessment in children aged 10 years or above was better than that in children aged less than 10 years.Interpretation:Assessment of pubertal development using a webbased self-assessment instrument could be less accurate among children aged less than 10 years,especially for girls' breast assessment.Therefore,self-assessment of pubertal development,especially for breast development,should be interpreted cautiously.